Amiri F, Haddad G, Garcia R
Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, University of Montreal, Canada.
J Hypertens. 1999 Feb;17(2):279-86. doi: 10.1097/00004872-199917020-00013.
To characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin-angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116.
One-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks.
Competitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116-treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density.
Angiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.
使用血管紧张素II拮抗剂氯沙坦和PD 123319，对大鼠非肾素依赖性单肾单夹高血压急性期的肾小球和球前血管血管紧张素II受体进行表征，并研究用血管紧张素转换酶抑制剂卡托普利或血管紧张素II受体拮抗剂TCV - 116阻断肾素 - 血管紧张素系统后它们的调节情况。
通过在雄性Sprague - Dawley大鼠的左肾动脉放置一个银夹（内径0.2毫米）并切除对侧肾脏，制备单肾单夹高血压模型。1、2或4周后，处死大鼠，纯化其肾小球和球前血管膜。使用特异性血管紧张素II拮抗剂进行竞争性结合研究。同样，在卡托普利或TCV - 116治疗2周前，让单肾单夹高血压发展2周。
竞争性结合研究表明，所有组的肾小球和球前血管上仅检测到血管紧张素II 1型（AT1）受体。1周和2周单肾单夹组的血管AT1受体密度显著更高，但与年龄匹配的单侧肾切除对照组相比，这些大鼠的肾小球受体密度没有差异。与未治疗和对照大鼠相比，卡托普利治疗的大鼠肾小球受体密度显著更高，而TCV - 116治疗的大鼠肾小球受体密度显著更低，但各组血管AT1受体密度均未检测到显著变化。
在高血压早期和肾素 - 血管紧张素系统阻断后，球前血管和肾小球上的血管紧张素II受体受到不同调节。高血压早期血管血管紧张素II受体上调，而肾小球血管紧张素II受体未上调。然而，在肾素 - 血管紧张素系统阻断后，肾小球而非血管血管紧张素II受体根据阻断类型受到不同调节。
